Yau Suk-Yu, Lee Thomas Ho-Yin, Li Ang, Xu Aimin, So Kwok-Fai
Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.
Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Front Neurosci. 2018 Oct 2;12:679. doi: 10.3389/fnins.2018.00679. eCollection 2018.
Streptozotocin (STZ)-induced diabetes impairs learning and memory performance and reduces adult hippocampal neurogenesis. Physical exercise brings beneficial effects. We have previously shown that adiponectin, an adipocyte-secreted hormone critically involved in the pathology of diabetes, is a key mediator for exercise-enhanced adult hippocampal neurogenesis. Here, we tested whether adiponectin is required for exercise to restore adult hippocampal neurogenesis in an animal model of diabetes. The findings showed that a single injection of 195 mg/kg STZ-induced diabetes significantly increased serum levels of corticosterone and reduced hippocampal adiponectin levels in adult mice. STZ injection also significantly reduced the number of Ki67 and doublecortin (DCX) positive cells and the ratio of co-labeling of DCX and bromodeoxyuridine (BrdU) in the hippocampal dentate region, indicating a decrease in adult hippocampal neurogenesis. Two-week voluntary wheel running significantly restored hippocampal neurogenesis in the diabetic wild-type mice, but not adiponectin knockout mice, indicating that adiponectin is critical for physical exercise to restore hippocampal adult neurogenesis in mice with diabetes. The results suggest that increasing adiponectin levels could be a therapeutic approach to restore hippocampal neurogenesis impairment in individuals with diabetes.
链脲佐菌素（STZ）诱导的糖尿病会损害学习和记忆能力，并减少成年海马神经发生。体育锻炼具有有益作用。我们之前已经表明，脂联素，一种在糖尿病病理过程中起关键作用的脂肪细胞分泌激素，是运动增强成年海马神经发生的关键介质。在此，我们测试了在糖尿病动物模型中，运动恢复成年海马神经发生是否需要脂联素。研究结果表明，单次注射195mg/kg STZ诱导的糖尿病显著提高了成年小鼠血清皮质酮水平，并降低了海马脂联素水平。注射STZ还显著减少了海马齿状区域中Ki67和双皮质素（DCX）阳性细胞的数量以及DCX与溴脱氧尿苷（BrdU）共标记的比例，表明成年海马神经发生减少。为期两周的自愿轮转跑步显著恢复了糖尿病野生型小鼠的海马神经发生，但对脂联素基因敲除小鼠无效，这表明脂联素对于体育锻炼恢复糖尿病小鼠的海马成年神经发生至关重要。结果表明，提高脂联素水平可能是恢复糖尿病个体海马神经发生损伤的一种治疗方法。
